Abstract Details

Title Novel Dentato-Olivo-Luysian Atrophy in a Greek Family

Topic Movement Disorders

Presentation(s) Movement Disorders Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 095

Objective To describe a unique Greek family with a clinical phenotype associated with a dentato-olivary-luysian atrophy overlapping with dentato-rubro-pallido-luysian atrophy (DRPLA) like pattern of neurological degeneration without an established genetic background.

Background DRPLA is a cause of spinocerebellar ataxia classified as a CAG repeat disorder. It presents with variable phenotypes including cerebellar ataxia, cognitive impairment, myoclonus, and seizures. Neuropathology shows dentatorubral and pallidoluysian systems degeneration. DRPLA mostly presents in Asians and is rarely seen outside of this population. A study of spinocerebellar ataxias in the Greek population found no cases of DRPLA.

Design/Methods Clinicopathological and genetic report of two siblings of Greek origin. Pathological studies including staining for Amyloid, α-synuclein, P-TDP-43, and P-Tau staining were performed. Genetic testing for common repeat disorders causing ataxia were carried out.

Results

Genetic testing for DRPLA, SCA 1,2,3,6,7,17 were negative. Progressive Myoclonic Epilepsy (PME) whole genome sequencing is pending. Both cases presented with a clinical phenotype of ataxia and seizures. The son of the female case was diagnosed with “Friedreich Ataxia” without genetic confirmation and passed away at age 14. On neuropathological evaluation, the two cases showed neuronal loss and gliosis predominating in the dentate nucleus, inferior olives, and subthalamic nucleus. Involvement of the substantia nigra was only seen in the younger male case. The older case had additional ischemic/hypoxic damage of neurons. P62 positive intranuclear inclusion bodies were not detected. Both cases showed Primary Age-Related Tauopathy (PART, Braak stage I and II, respectively) but lack of other tau-, or α-synuclein- or TDP-43 proteinopathies.

Conclusions We describe an autosomal dominant presentation of a progressive ataxia and epilepsy disorder with a dentato-olivary-luysian pattern of degeneration. This pattern is reminiscent of the DRPLA pattern described in Asian individuals and associated with CAG repeats, which was negative in this family. The childhood onset in successive generation could suggest an anticipation phenomena.

Authors/Disclosures
Sohaila A. Alshimemeri, MD (King Saud University) PRESENTER	Dr. Alshimemeri has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Renato P. Munhoz, MD, PhD	Dr. Munhoz has nothing to disclose.
Elizabeth Slow, MD, PhD	Dr. Slow has nothing to disclose.
Anthony E. Lang, MD, F�鶹��ýӳ�� (Toronto Western Hospital)	Dr. Lang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AbbVie, Amylyx, Aprinoia, Biogen, BioAdvance, Biohaven, BioVie, BlueRock, BMS, Denali, Janssen, Lilly, Pharma 2B, Sun Pharma, and UCB. Dr. Lang has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for medicolegal cases related to paraquat. The institution of Dr. Lang has received research support from AbbVie. Dr. Lang has received intellectual property interests from a discovery or technology relating to health care. Dr. Lang has received publishing royalties from a publication relating to health care.
	No disclosure on file

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